American Journal of Epidemiology 2009 169(2):195-205; doi:10.1093/aje/kwn309
Determinants of the Incidence of Childhood Asthma: A Two-Stage Case-Control Study
Marie-Josée Martel, Évelyne Rey, Jean-Luc Malo, Sylvie Perreault, Marie-France Beauchesne, Amélie Forget and Lucie Blais
Correspondence to Dr. Lucie Blais, Faculté de pharmacie, Université de Montréal, C.P. 6128, succursale Centre-ville, Montréal, Québec H3C 3J7, Canada (e-mail: lucie.blais@umontreal.ca
Extensive literature exists on potential risk factors for childhood asthma. To the authors’ knowledge, no investigators have yet attempted to disentangle the effects of those determinants within a single study setting. The authors aimed to evaluate the independent effects of 47 potential determinants (from the prenatal, perinatal, and childhood periods) of asthma development in children within the first 10 years of life. From a Canadian birth cohort of 26,265 children (1990–2002), a 2-stage case-control study was conducted. In the first stage, 20 controls per case were selected from 3 administrative databases. In the second stage, selected mothers were mailed questionnaires for assessment of additional determinants. Increased risks of childhood asthma were found for 1 previous diagnosis of bronchopulmonary disease and atopic dermatitis in the child, oxygen administration after birth, prescription of antibiotics within the first 6 months of life, male gender, asthma during pregnancy, use of antibiotics during pregnancy, maternal receipt of social aid, paternal asthma, and asthma in siblings. Protective effects included use of intranasal corticosteroids during pregnancy, having a wood-burning fireplace, having pets in the home prior to the index date, breastfeeding, and day-care attendance. This study allowed the authors to identify, within a single setting, the most influential determinants of childhood asthma among 47 predictors assessed for the prenatal, perinatal, and childhood periods.
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BrooklynDodger(s) comment: Another mining of a huge surveillance cohort. For those studying environmental causation of childhood asthma, a great value of this publication is compiling all the other associations found in the literature. It's tempting to ascribe some mechanism to the protective effect of pets in the home. But the Dodger(s) fear(s) that studies of this type are subject to lots of uncontrolled confounding.
Saturday, January 31, 2009
Friday, January 30, 2009
Chlorinated Solvent Exposure Associated Increased Hematopoietic Tumors
American Journal of Epidemiology 2009 169(2):176-185; doi:10.1093/aje/kwn300 Occupational Exposure to Solvents and Risk of Non-Hodgkin Lymphoma in Connecticut Women
Rong Wang, Yawei Zhang, Qing Lan, Theodore R. Holford, Brian Leaderer, Shelia Hoar Zahm, Peter Boyle, Mustafa Dosemeci, Nathaniel Rothman, Yong Zhu, Qin Qin and Tongzhang Zheng
Correspondence to Dr. Tongzhang Zheng, Yale School of Public Health, 60 College Street, LEPH 427, P.O. Box 208034, New Haven, CT 06520-8034 (e-mail: tongzhang.zheng@yale.edu
A population-based case-control study involving 601 incident cases of non-Hodgkin lymphoma (NHL) and 717 controls was conducted in 1996–2000 among Connecticut women to examine associations with exposure to organic solvents. A job-exposure matrix was used to assess occupational exposures. Increased risk of NHL was associated with occupational exposure to chlorinated solvents (odds ratio (OR) = 1.4, 95% confidence interval (CI): 1.1, 1.8) and carbon tetrachloride (OR = 2.3, 95% CI: 1.3, 4.0). Those ever exposed to any organic solvent in work settings had a borderline increased risk of NHL (OR = 1.3, 95% CI: 1.0, 1.6); moreover, a significantly increased risk was observed for those with average probability of exposure to any organic solvent at medium-high level (OR = 1.5, 95% CI: 1.1, 1.9). A borderline increased risk was also found for ever exposure to formaldehyde (OR = 1.3, 95% CI: 1.0, 1.7) in work settings. Risk of NHL increased with increasing average intensity (P = 0.01), ...
Rong Wang, Yawei Zhang, Qing Lan, Theodore R. Holford, Brian Leaderer, Shelia Hoar Zahm, Peter Boyle, Mustafa Dosemeci, Nathaniel Rothman, Yong Zhu, Qin Qin and Tongzhang Zheng
Correspondence to Dr. Tongzhang Zheng, Yale School of Public Health, 60 College Street, LEPH 427, P.O. Box 208034, New Haven, CT 06520-8034 (e-mail: tongzhang.zheng@yale.edu
A population-based case-control study involving 601 incident cases of non-Hodgkin lymphoma (NHL) and 717 controls was conducted in 1996–2000 among Connecticut women to examine associations with exposure to organic solvents. A job-exposure matrix was used to assess occupational exposures. Increased risk of NHL was associated with occupational exposure to chlorinated solvents (odds ratio (OR) = 1.4, 95% confidence interval (CI): 1.1, 1.8) and carbon tetrachloride (OR = 2.3, 95% CI: 1.3, 4.0). Those ever exposed to any organic solvent in work settings had a borderline increased risk of NHL (OR = 1.3, 95% CI: 1.0, 1.6); moreover, a significantly increased risk was observed for those with average probability of exposure to any organic solvent at medium-high level (OR = 1.5, 95% CI: 1.1, 1.9). A borderline increased risk was also found for ever exposure to formaldehyde (OR = 1.3, 95% CI: 1.0, 1.7) in work settings. Risk of NHL increased with increasing average intensity (P = 0.01), ...
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BooklynDodger(s) comment: So many issues, so many cell types, so little time to write coherently. This study is about hematopoietic tumors in people.
For lymphomae, there's Hodgkins Disease and non-Hodgkins Lymphoma. NHL has some subtypes. For leukemiae we have 4 kinds - acute and chronic types for myelogenous and lymphocytic. Also subtypes. There's also multiple myeloma. Each has contrasting age and gender patterns. Ultimately these tumors all come from cell lines tracking back to a common stem cell, but there's several generations of intermediate stem cells from which the tumor might arise. Logically, the stem cell is the locus of attack. Should each be considered independently, or lumped together? Does clear evidence for an assocation with one cell type identify a hazard for all the other cell types?
Finally, the picture in laboratory studies is also muddled. Benzene is the SQN agent for leukemia in people. In the bioassay, it's a very potent carcinogen, but at many tumor sites not including leukemia:
"Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene for male F344/N rats, for female F344/N rats, for male B6C3F1 mice, and for female B6C3F1 mice. For male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. For female rats, benzene caused increased incidences of Zymbal gland carcinomas and squamous cell papillomas and squamous cell carcinomas of the oral cavity. For male mice, benzene caused increased incidences of Zymbal gland squamous cell carcinomas, malignant lymphomas, alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas (combined), harderian gland adenomas, and squamous cell carcinomas of the preputial gland. For female mice, benzene caused increased incidences of malignant lymphomas, ovarian granulosa cell tumors, ovarian benign mixed tumors, carcinomas and carcinosarcomas of the mammary gland, alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas, and Zymbal gland squamous cell carcinomas. Dose-related lymphocytopenia was observed for male and female F344/N rats and male and female B6C3F1 mice."
For perchloroethylene, the picture was different:
"Under the conditions of these 2-year inhalation studies, there was clear evidence of carcinogenicity of tetrachloroethylene for male F344/N rats as shown by an increased incidence of mononuclear cell leukemia and uncommon renal tubular cell neoplasms. There was some evidence of carcinogenicity of tetrachloroethylene for female F344/N rats as shown by increased incidences of mononuclear cell leukemia. There was clear evidence of carcinogenicity for B6C3F1 mice as shown by increased incidences of both hepatocellular adenomas and carcinomas in males and of hepatocellular carcinomas in females."
Thursday, January 29, 2009
Living Near A Steel Mill Increases Metabolites of Carcinogens in Children
Cancer Epidemiology Biomarkers & Prevention 18, 96-101, January 1, 2009.
Seasonal and Regional Contributors of 1-Hydroxypyrene among Children near a Steel Mill
Mi-Sun Lee1, Ki-Do Eum1, Kiyoung Lee1, Ho Kim2 and Domyung Paek1
Departments of 1 Environmental Health and 2 Biostatistics, Graduate School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea
Requests for reprints: Domyung Paek, Department of Environmental Health, Graduate School of Public Health and Institute of Health and Environment, Seoul National University, 28 Yeongeon-Dong, Jongno-Gu, Seoul 110-460, Republic of Korea. Phone: 82-2-740-8886 ; Fax: 82-2-743-8240. E-mail: paekdm@snu.ac.kr
Urinary 1-hydroxypyrene (1-OHP) is a biomarker of exposure to polycyclic aromatic hydrocarbons (PAH). Effect of residence on children's PAH exposure was reported among children living near a polluted area. Instead of a snapshot assessment, however, a temporal history of exposure characteristics needs to be assessed in the studies of chronic disease development such as cancer. The urinary 1-OHP measurements were repeated to determine regional effect of ambient air pollution on 1-OHP levels over extended periods. Two sites were chosen: (a) one site located near the steel mill ("nearby" site) and (b) the other site located at a longer distance from the mill ("remote" site). Spot urinary 1-OHP levels were measured from 72 children for 3 consecutive days per month, repeated over 9-month period. Compared with remote site, the nearby site had increased the urinary 1-OHP level by 62.3% [95% confidence interval (95% CI), 39.8-88.3%]. Other statistically significant factors that contributed to the level include sex [16.5% (95% CI, 1.2-34.1%) higher for girls than boys], consumption of charbroiled meat [16.5% (95% CI, 1.1-34.2%) higher], and an increase in PM10 [10.1% (95% CI, 4.8-15.7%) higher for the interquartile range increment]. Controlling for covariates, the 1-OHP levels were increased in the summer and fall compared with winter. The magnitude of the effects of both seasons had diminished after adjusting for PM10. This is the first report providing seasonal and regional contributors to environmental PAH exposure, assessed by urinary 1-OHP, with higher 1-OHP levels during summer when ambient pollution was also high.
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BrooklynDodger(s) Comments: Neighborhood or census tract epidemiology in relation to environmental contaminants is problemmatic. Politically, we always fight the problem that significant public health risks - occupationally 1 in a 1000 and below, environmentally lower than that - are below the limit that can be directly observed in a human population. Remember, the lifetime risk of cancer at any site is upwards of 300 per 1000, for lung cancer upwards of 50 per thousand. A null study rules out only the most dramatic of risks in a locality. [There are obstacles beyond this statisical problem as well.]
Korean colleagues have identified an increased exposure through biological monitoring for carcinogen metabolites. The Dodger(s) would have liked to see some exposure monitoring to support the study. The Dodger(s) also confess to not reading the full paper, so the Dodger(s) don't know if the "steel mill" included a coke oven, which would be a major source of PAC's (not political action committees, but polynuclear aromatic compounds, a more inclusive term than PAH's)
Seasonal and Regional Contributors of 1-Hydroxypyrene among Children near a Steel Mill
Mi-Sun Lee1, Ki-Do Eum1, Kiyoung Lee1, Ho Kim2 and Domyung Paek1
Departments of 1 Environmental Health and 2 Biostatistics, Graduate School of Public Health and Institute of Health and Environment, Seoul National University, Seoul, Republic of Korea
Requests for reprints: Domyung Paek, Department of Environmental Health, Graduate School of Public Health and Institute of Health and Environment, Seoul National University, 28 Yeongeon-Dong, Jongno-Gu, Seoul 110-460, Republic of Korea. Phone: 82-2-740-8886 ; Fax: 82-2-743-8240. E-mail: paekdm@snu.ac.kr
Urinary 1-hydroxypyrene (1-OHP) is a biomarker of exposure to polycyclic aromatic hydrocarbons (PAH). Effect of residence on children's PAH exposure was reported among children living near a polluted area. Instead of a snapshot assessment, however, a temporal history of exposure characteristics needs to be assessed in the studies of chronic disease development such as cancer. The urinary 1-OHP measurements were repeated to determine regional effect of ambient air pollution on 1-OHP levels over extended periods. Two sites were chosen: (a) one site located near the steel mill ("nearby" site) and (b) the other site located at a longer distance from the mill ("remote" site). Spot urinary 1-OHP levels were measured from 72 children for 3 consecutive days per month, repeated over 9-month period. Compared with remote site, the nearby site had increased the urinary 1-OHP level by 62.3% [95% confidence interval (95% CI), 39.8-88.3%]. Other statistically significant factors that contributed to the level include sex [16.5% (95% CI, 1.2-34.1%) higher for girls than boys], consumption of charbroiled meat [16.5% (95% CI, 1.1-34.2%) higher], and an increase in PM10 [10.1% (95% CI, 4.8-15.7%) higher for the interquartile range increment]. Controlling for covariates, the 1-OHP levels were increased in the summer and fall compared with winter. The magnitude of the effects of both seasons had diminished after adjusting for PM10. This is the first report providing seasonal and regional contributors to environmental PAH exposure, assessed by urinary 1-OHP, with higher 1-OHP levels during summer when ambient pollution was also high.
>>>>>>>>>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) Comments: Neighborhood or census tract epidemiology in relation to environmental contaminants is problemmatic. Politically, we always fight the problem that significant public health risks - occupationally 1 in a 1000 and below, environmentally lower than that - are below the limit that can be directly observed in a human population. Remember, the lifetime risk of cancer at any site is upwards of 300 per 1000, for lung cancer upwards of 50 per thousand. A null study rules out only the most dramatic of risks in a locality. [There are obstacles beyond this statisical problem as well.]
Korean colleagues have identified an increased exposure through biological monitoring for carcinogen metabolites. The Dodger(s) would have liked to see some exposure monitoring to support the study. The Dodger(s) also confess to not reading the full paper, so the Dodger(s) don't know if the "steel mill" included a coke oven, which would be a major source of PAC's (not political action committees, but polynuclear aromatic compounds, a more inclusive term than PAH's)
Wednesday, January 28, 2009
Does Alzheimer's Really Increase with Duration of Living Near Power Lines?
American Journal of Epidemiology 2009 169(2):167-175; doi:10.1093/aje/kwn
Residence Near Power Lines and Mortality From Neurodegenerative Diseases: Longitudinal Study of the Swiss Population
Anke Huss, Adrian Spoerri, Matthias Egger, Martin Röösli and for the Swiss National Cohort Study
Correspondence to Dr. Anke Huss, Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, CH-3012 Bern, Switzerland (e-mail: ahuss@ispm.unibe.ch
The relation between residential magnetic field exposure from power lines and mortality from neurodegenerative conditions was analyzed among 4.7 million persons of the Swiss National Cohort (linking mortality and census data), covering the period 2000–2005. Cox proportional hazard models were used to analyze the relation of living in the proximity of 220–380 kV power lines and the risk of death from neurodegenerative diseases, with adjustment for a range of potential confounders. Overall, the adjusted hazard ratio for Alzheimer's disease in persons living within 50 m of a 220–380 kV power line was 1.24 (95% confidence interval (CI): 0.80, 1.92) compared with persons who lived at a distance of 600 m or more. There was a dose-response relation with respect to years of residence in the immediate vicinity of power lines and Alzheimer's disease: Persons living at least 5 years within 50 m had an adjusted hazard ratio of 1.51 (95% CI: 0.91, 2.51), increasing to 1.78 (95% CI: 1.07, 2.96) with at least 10 years and to 2.00 (95% CI: 1.21, 3.33) with at least 15 years. The pattern was similar for senile dementia. There was little evidence for an increased risk of amyotrophic lateral sclerosis, Parkinson's disease, or multiple sclerosis.
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BrooklynDodger(s) comment: The Dodger(s) confess to not having read the full text. The Dodger(s) has (have) not been excited about EMF and RF exposures, although the subject continues to be studied, with associations reported. Mashups of geographic and health data permit a proliferation of hypothesis raising studies.
There's power in the metaphor of electrical activity and brain waves. The main electrical activity is neurons. It's worth remembering that the main locus of these adverse effects, and CNS cancers, is from the glial cells, which are not particularly electrical. Some of the neuronal damage also arises from damage to glial cells and other supportive tissue.
Residence Near Power Lines and Mortality From Neurodegenerative Diseases: Longitudinal Study of the Swiss Population
Anke Huss, Adrian Spoerri, Matthias Egger, Martin Röösli and for the Swiss National Cohort Study
Correspondence to Dr. Anke Huss, Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, CH-3012 Bern, Switzerland (e-mail: ahuss@ispm.unibe.ch
The relation between residential magnetic field exposure from power lines and mortality from neurodegenerative conditions was analyzed among 4.7 million persons of the Swiss National Cohort (linking mortality and census data), covering the period 2000–2005. Cox proportional hazard models were used to analyze the relation of living in the proximity of 220–380 kV power lines and the risk of death from neurodegenerative diseases, with adjustment for a range of potential confounders. Overall, the adjusted hazard ratio for Alzheimer's disease in persons living within 50 m of a 220–380 kV power line was 1.24 (95% confidence interval (CI): 0.80, 1.92) compared with persons who lived at a distance of 600 m or more. There was a dose-response relation with respect to years of residence in the immediate vicinity of power lines and Alzheimer's disease: Persons living at least 5 years within 50 m had an adjusted hazard ratio of 1.51 (95% CI: 0.91, 2.51), increasing to 1.78 (95% CI: 1.07, 2.96) with at least 10 years and to 2.00 (95% CI: 1.21, 3.33) with at least 15 years. The pattern was similar for senile dementia. There was little evidence for an increased risk of amyotrophic lateral sclerosis, Parkinson's disease, or multiple sclerosis.
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BrooklynDodger(s) comment: The Dodger(s) confess to not having read the full text. The Dodger(s) has (have) not been excited about EMF and RF exposures, although the subject continues to be studied, with associations reported. Mashups of geographic and health data permit a proliferation of hypothesis raising studies.
There's power in the metaphor of electrical activity and brain waves. The main electrical activity is neurons. It's worth remembering that the main locus of these adverse effects, and CNS cancers, is from the glial cells, which are not particularly electrical. Some of the neuronal damage also arises from damage to glial cells and other supportive tissue.
Tuesday, January 27, 2009
Monday, January 26, 2009
Evidence That Work Stress Causes Heart Disease Through Direct and Indirect Pathways
European Heart Journal 2008 29(5):640-648
Work stress and coronary heart disease: what are the mechanisms?
Tarani Chandola1,*, Annie Britton1, Eric Brunner1, Harry Hemingway1, Marek Malik2, Meena Kumari1, Ellena Badrick1, Mika Kivimaki1 and Michael Marmot1
1 Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 6BT, UK
2 Department of Cardiac and Vascular Sciences, St George’s University of London, London, UK
* Corresponding author. Tel: +44 20 7679 5629 , Fax: +44 20 7813 0242. Email: t.chandola@ucl.ac.uk
See page 579 for the editorial comment on this article (doi:10.1093/eurheartj/ehm641)
Aims: To determine the biological and behavioural factors linking work stress with coronary heart disease (CHD).
Methods and results: A total of 10 308 London-based male and female civil servants aged 35–55 at phase 1 (1985–88) of the Whitehall II study were studied. Exposures included work stress (assessed at phases 1 and 2), and outcomes included behavioural risk factors (phase 3), the metabolic syndrome (phase 3), heart rate variability, morning rise in cortisol (phase 7), and incident CHD (phases 2–7) on the basis of CHD death, non-fatal myocardial infarction, or definite angina. Chronic work stress was associated with CHD and this association was stronger among participants aged under 50 (RR 1.68, 95% CI 1.17–2.42). There were similar associations between work stress and low physical activity, poor diet, the metabolic syndrome, its components, and lower heart rate variability. Cross-sectionally, work stress was associated with a higher morning rise in cortisol. Around 32% of the effect of work stress on CHD was attributable to its effect on health behaviours and the metabolic syndrome.
Conclusion: Work stress may be an important determinant of CHD among working-age populations, which is mediated through indirect effects on health behaviours and direct effects on neuroendocrine stress pathways.
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BrooklynDodger(s) comment: Being British, these findings may be culture bound, but Whitehall II seems to be the only game in the world, not just in town. The Dodger(s) confess not to have read the full text. The Dodger(s) haven't figured out the 32% - seems like health behaviors are a cause and metabolic syndrome an intermediate outcome. The generalized lesson is that preventing health risk behaviors can best be accomplished by abating the causes, and one of these causes is work related psychosocial stress.
Work stress and coronary heart disease: what are the mechanisms?
Tarani Chandola1,*, Annie Britton1, Eric Brunner1, Harry Hemingway1, Marek Malik2, Meena Kumari1, Ellena Badrick1, Mika Kivimaki1 and Michael Marmot1
1 Department of Epidemiology and Public Health, University College London, 1-19 Torrington Place, London WC1E 6BT, UK
2 Department of Cardiac and Vascular Sciences, St George’s University of London, London, UK
* Corresponding author. Tel: +44 20 7679 5629 , Fax: +44 20 7813 0242. Email: t.chandola@ucl.ac.uk
See page 579 for the editorial comment on this article (doi:10.1093/eurheartj/ehm641)
Aims: To determine the biological and behavioural factors linking work stress with coronary heart disease (CHD).
Methods and results: A total of 10 308 London-based male and female civil servants aged 35–55 at phase 1 (1985–88) of the Whitehall II study were studied. Exposures included work stress (assessed at phases 1 and 2), and outcomes included behavioural risk factors (phase 3), the metabolic syndrome (phase 3), heart rate variability, morning rise in cortisol (phase 7), and incident CHD (phases 2–7) on the basis of CHD death, non-fatal myocardial infarction, or definite angina. Chronic work stress was associated with CHD and this association was stronger among participants aged under 50 (RR 1.68, 95% CI 1.17–2.42). There were similar associations between work stress and low physical activity, poor diet, the metabolic syndrome, its components, and lower heart rate variability. Cross-sectionally, work stress was associated with a higher morning rise in cortisol. Around 32% of the effect of work stress on CHD was attributable to its effect on health behaviours and the metabolic syndrome.
Conclusion: Work stress may be an important determinant of CHD among working-age populations, which is mediated through indirect effects on health behaviours and direct effects on neuroendocrine stress pathways.
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BrooklynDodger(s) comment: Being British, these findings may be culture bound, but Whitehall II seems to be the only game in the world, not just in town. The Dodger(s) confess not to have read the full text. The Dodger(s) haven't figured out the 32% - seems like health behaviors are a cause and metabolic syndrome an intermediate outcome. The generalized lesson is that preventing health risk behaviors can best be accomplished by abating the causes, and one of these causes is work related psychosocial stress.
Sunday, January 25, 2009
Job Strain Causes Obesity? Obesity causes...
American Journal of Epidemiology 2007 165(7):828-837
Prospective Effect of Job Strain on General and Central Obesity in the Whitehall II Study
Eric J. Brunner, Tarani Chandola and Michael G. Marmot
From the Department of Epidemiology and Public Health, Royal Free and University College London Medical School, London, England
Correspondence to Dr. Eric J. Brunner, Department of Epidemiology and Public Health, Royal Free and University College London Medical School, 1-19 Torrington Place, London WC1E 6BT, England (e-mail: e.brunner{at}ucl.ac.uk).
Positive energy balance is the major cause of obesity, and chronic stress may be a contributory factor. The authors examined cumulative work stress, using the Job Strain Questionnaire on four occasions, as a predictor of obesity in a prospective 19-year study of 6,895 men and 3,413 women (aged 35–55 years) in the Whitehall II cohort in London, United Kingdom (baseline: 1985–1988). A dose-response relation was found between work stress and risk of general obesity (body mass index 30 kg/m2) and central obesity (waist circumference >102 cm in men, >88 cm in women) that was largely independent of covariates. The imputed odds ratios of body mass index obesity for one, two, and three or more reports of work stress adjusted for age, sex, and social position were 1.17, 1.24, and 1.73 (trend p < color="#990000">This study provides prospective, population-based evidence that chronic work stress predicts general and central obesity.
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BrooklynDodger(s) comment: The "obsesity epidemic" is in part a moral panic in which persons lacking the will to eat less are blamed for the health problems which arise among those in the upper range of obese (BMI > 30) and extremely obese (BMI > 35). The next step will be taking their health insurance away, or not agreeing to national health security.
[You can calculate your BMI at http://www.consumer.gov/weightloss/bmi.htm
For a 6 footer (gender underfined), 185 lbs begins overweight and 220 obese.]
This paper finds that job stress precedes increased caloric intake and increased weight. Intervening of job stress thus has a quantitive relationship to reduced mortality and morbidity.
Prospective Effect of Job Strain on General and Central Obesity in the Whitehall II Study
Eric J. Brunner, Tarani Chandola and Michael G. Marmot
From the Department of Epidemiology and Public Health, Royal Free and University College London Medical School, London, England
Correspondence to Dr. Eric J. Brunner, Department of Epidemiology and Public Health, Royal Free and University College London Medical School, 1-19 Torrington Place, London WC1E 6BT, England (e-mail: e.brunner{at}ucl.ac.uk).
Positive energy balance is the major cause of obesity, and chronic stress may be a contributory factor. The authors examined cumulative work stress, using the Job Strain Questionnaire on four occasions, as a predictor of obesity in a prospective 19-year study of 6,895 men and 3,413 women (aged 35–55 years) in the Whitehall II cohort in London, United Kingdom (baseline: 1985–1988). A dose-response relation was found between work stress and risk of general obesity (body mass index 30 kg/m2) and central obesity (waist circumference >102 cm in men, >88 cm in women) that was largely independent of covariates. The imputed odds ratios of body mass index obesity for one, two, and three or more reports of work stress adjusted for age, sex, and social position were 1.17, 1.24, and 1.73 (trend p < color="#990000">This study provides prospective, population-based evidence that chronic work stress predicts general and central obesity.
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BrooklynDodger(s) comment: The "obsesity epidemic" is in part a moral panic in which persons lacking the will to eat less are blamed for the health problems which arise among those in the upper range of obese (BMI > 30) and extremely obese (BMI > 35). The next step will be taking their health insurance away, or not agreeing to national health security.
[You can calculate your BMI at http://www.consumer.gov/weightloss/bmi.htm
For a 6 footer (gender underfined), 185 lbs begins overweight and 220 obese.]
This paper finds that job stress precedes increased caloric intake and increased weight. Intervening of job stress thus has a quantitive relationship to reduced mortality and morbidity.
Saturday, January 24, 2009
What's Shaking - A Convenient Measurement of Vibration Could be Used for Standards
International Journal of Industrial Ergonomics
Volume 39, Issue 1, January 2009, Pages 174-184
An investigation on characteristics of the vibration transmitted to wrist and elbow in the operation of impact wrenches
X.S. Xu, a, , D.E. Welcomea, T.W. McDowella, C. Warrena and R.G. Donga
aEngineering & Control Technology Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA
Abstract
To help assess the risk of the vibration exposure during impact wrench operation and to develop a convenient and effective method to monitor and control the exposure, this study aims to investigate the characteristics of the vibrations transmitted to the wrist and elbow in the operation and to evaluate the on-the-wrist and on-the-elbow vibration measurement methods. Six subjects participated in the experiment. Each of them used 15 impact wrenches on a simulated workstation. Tri-axial accelerations at three locations (tool handle, wrist, and elbow) and the tool effective torques were measured and used in the evaluations. Results confirm that the severity of the vibration exposure generally depends on tool and individual, and that the vibrations measured at wrist and elbow reflect the influences of both factors. This study also found that the accelerations measured at the wrist and elbow are correlated with the ISO frequency-weighted tool acceleration. The fundamental resonance of the hand-arm system in the range of 16–50 Hz is well reflected in the vibration measured at the wrist. The results also demonstrate that vibration exposure duration can be reliably detected from the wrist vibration data. Moreover, the wrist vibration is suggestively correlated with the torque of the pneumatic impact wrenches. These findings suggest that the measurement of the wrist vibration can be used as an alternative approach to perform the exposure risk assessment and to monitor and control the exposures in the operation of the impact wrenches.
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BrooklynDodger(s) comment: An unacceptable fraction of people who use powered hand tools in routine assembly operations suffer cumulative trauma disorders. Most quantitative standards for limiting exposure are unprotective because they are aimed at event windows of a year or so - the most anyone is in an unchanged work station - rather than a 30 to 45 year career. Standards also suffer from the variety of features of exposure that may be measured, usually measuring some features means omitting others. Then, investigators compete incomplete exposure schemes against retrospective short term outcomes. European standards for tools exist, based on acceleration. A large fraction of current tools violate these standards, which limits the ability to see exposure response.
This investigation proposes a method of measuring the interaction of force with worker characteristics. Laboratory studies generate a lot of numbers - 6 workers x 15 tools x however many parameters measured.
Volume 39, Issue 1, January 2009, Pages 174-184
An investigation on characteristics of the vibration transmitted to wrist and elbow in the operation of impact wrenches
X.S. Xu, a, , D.E. Welcomea, T.W. McDowella, C. Warrena and R.G. Donga
aEngineering & Control Technology Branch, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA
Abstract
To help assess the risk of the vibration exposure during impact wrench operation and to develop a convenient and effective method to monitor and control the exposure, this study aims to investigate the characteristics of the vibrations transmitted to the wrist and elbow in the operation and to evaluate the on-the-wrist and on-the-elbow vibration measurement methods. Six subjects participated in the experiment. Each of them used 15 impact wrenches on a simulated workstation. Tri-axial accelerations at three locations (tool handle, wrist, and elbow) and the tool effective torques were measured and used in the evaluations. Results confirm that the severity of the vibration exposure generally depends on tool and individual, and that the vibrations measured at wrist and elbow reflect the influences of both factors. This study also found that the accelerations measured at the wrist and elbow are correlated with the ISO frequency-weighted tool acceleration. The fundamental resonance of the hand-arm system in the range of 16–50 Hz is well reflected in the vibration measured at the wrist. The results also demonstrate that vibration exposure duration can be reliably detected from the wrist vibration data. Moreover, the wrist vibration is suggestively correlated with the torque of the pneumatic impact wrenches. These findings suggest that the measurement of the wrist vibration can be used as an alternative approach to perform the exposure risk assessment and to monitor and control the exposures in the operation of the impact wrenches.
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BrooklynDodger(s) comment: An unacceptable fraction of people who use powered hand tools in routine assembly operations suffer cumulative trauma disorders. Most quantitative standards for limiting exposure are unprotective because they are aimed at event windows of a year or so - the most anyone is in an unchanged work station - rather than a 30 to 45 year career. Standards also suffer from the variety of features of exposure that may be measured, usually measuring some features means omitting others. Then, investigators compete incomplete exposure schemes against retrospective short term outcomes. European standards for tools exist, based on acceleration. A large fraction of current tools violate these standards, which limits the ability to see exposure response.
This investigation proposes a method of measuring the interaction of force with worker characteristics. Laboratory studies generate a lot of numbers - 6 workers x 15 tools x however many parameters measured.
Friday, January 23, 2009
Risk Behavior among Younger Drivers
Accident Analysis & PreventionVolume 41, Issue 1, January 2009, Pages 25-35
The role of risk-propensity in the risky driving of younger drivers
Julie Hatfield, a, and Ralston Fernandesa,
aNSW Injury Risk Management Research Centre, The University of NSW, NSW 2052, Australia
Abstract
Young drivers are over-represented in road injury statistics, partly because they engage in more risky driving than older people. Although it is assumed that younger people have greater risk-propensity, defined as a positive attitude to risk, relevant theory is imprecise and relevant research is clouded by inappropriate measures. 89 participants aged 16–25 and 110 participants aged over 35 were recruited outside motor registries. Participants completed a battery of questionnaires including Rohrmann’s [Rohrmann, B. 2004. Risk attitude scales: concepts and questionnaires. Project report. Available at http://www.rohrmannresearch.net/pdfs/rohrmann-racreport.pdf (last accessed 12th February 2008)] measures of risk-aversion, risk-propensity, and risk-related motives for risky driving, as well as measures of risk-perception and risky driving. Compared to older drivers, younger drivers demonstrated lower risk-aversion, and higher propensity for taking accident risks, as well as stronger motives for risky driving in relation to experience-seeking, excitement, sensation-seeking, social influence, prestige-seeking, confidence/familiarity, underestimation of risk, irrelevance of risk, “letting off steam”, and “getting there quicker”. Further, these variables were associated with risky driving. Some evidence was observed for the possibility that risk propensity moderates the relationship between perceived risk and risky behaviour. These results suggest approaches to targeting the “young driver problem”.
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BrooklynDodger(s) comment: Most injury control studies are related to traffic rather than occupational studies. AAP is a leading journal. The Dodger(s) believe(s) that in general, injury control schemes based on attention state, risk perception, reaction time, judgement of exposed persons are doomed to limited success without higher levels of controls. Nevertheless, interest in the role of attitudes remains high. Extending traffic related risks to broader occupational risks is problemmatic because the environment and equipment are subject to such limited controls. The Dodger(s) question(s) the limits of attitude intervention when drivers of all ages brag about speeding and beating tickets or getting home safe DWP (driving while plowed.)
This investigation is culturally bound by Australian society, not known for risk adversion or introversion.
The Dodger(s) confess to failing to read the full text to find the definition of self reported "risky driving" which is the key endpoint in this paper. The correlation between motives and attitudes seems confounded, but reported risk actions is of value.
The role of risk-propensity in the risky driving of younger drivers
Julie Hatfield, a, and Ralston Fernandesa,
aNSW Injury Risk Management Research Centre, The University of NSW, NSW 2052, Australia
Abstract
Young drivers are over-represented in road injury statistics, partly because they engage in more risky driving than older people. Although it is assumed that younger people have greater risk-propensity, defined as a positive attitude to risk, relevant theory is imprecise and relevant research is clouded by inappropriate measures. 89 participants aged 16–25 and 110 participants aged over 35 were recruited outside motor registries. Participants completed a battery of questionnaires including Rohrmann’s [Rohrmann, B. 2004. Risk attitude scales: concepts and questionnaires. Project report. Available at http://www.rohrmannresearch.net/pdfs/rohrmann-racreport.pdf (last accessed 12th February 2008)] measures of risk-aversion, risk-propensity, and risk-related motives for risky driving, as well as measures of risk-perception and risky driving. Compared to older drivers, younger drivers demonstrated lower risk-aversion, and higher propensity for taking accident risks, as well as stronger motives for risky driving in relation to experience-seeking, excitement, sensation-seeking, social influence, prestige-seeking, confidence/familiarity, underestimation of risk, irrelevance of risk, “letting off steam”, and “getting there quicker”. Further, these variables were associated with risky driving. Some evidence was observed for the possibility that risk propensity moderates the relationship between perceived risk and risky behaviour. These results suggest approaches to targeting the “young driver problem”.
>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: Most injury control studies are related to traffic rather than occupational studies. AAP is a leading journal. The Dodger(s) believe(s) that in general, injury control schemes based on attention state, risk perception, reaction time, judgement of exposed persons are doomed to limited success without higher levels of controls. Nevertheless, interest in the role of attitudes remains high. Extending traffic related risks to broader occupational risks is problemmatic because the environment and equipment are subject to such limited controls. The Dodger(s) question(s) the limits of attitude intervention when drivers of all ages brag about speeding and beating tickets or getting home safe DWP (driving while plowed.)
This investigation is culturally bound by Australian society, not known for risk adversion or introversion.
The Dodger(s) confess to failing to read the full text to find the definition of self reported "risky driving" which is the key endpoint in this paper. The correlation between motives and attitudes seems confounded, but reported risk actions is of value.
Thursday, January 22, 2009
Houdini Risk Assessments Discussed
Human and Ecological Risk Assessment: An International Journal,
Volume
9, Issue 5 September 2003 , pages 1129 - 1143
Does the Emperor Have Any Clothes: Using Mechanistic Information or Doing Houdini Risk Assessments?
Author: Mirer, Franklin E.1
Abstract: Risk assessment research rarely quells controversy. Mega-mouse, and mega-rat, experiments contradicted a threshold for carcinogenesis, yet thresholds are still argued. High to low dose continuity of response from cigarette smoking to environmental tobacco smoke, and from occupational asbestos exposure to take-home asbestos, contradict thresholds in people. Nevertheless, mechanistic hypotheses allege "Houdini Risk Assessments", which make risks disappear or allow industries to escape from protecting workers. Despite concerns for animal-to-human extrapolations, priority occupational exposures with sufficient or substantial evidence of carcinogenicity in people not addressed by new exposure limits include silica, sulfuric acid mist, chromates, diesel particulate matter, particulate matter generally, metalworking fluids, welding fume, and formaldehyde. "Houdini Risk Assessments" are exercises in "anti-hypothesis generation": ignore selected tumor sites and types; ignore data from people (as with formaldehyde and diesel); choose the most resistant species in laboratory tests; select biochemical parameters in which the most resistant species resembles people; assume a mechanism that gives threshold or steep exposure response for carcinogenic effect; and reduce estimated people risk by the parameter ratio to the most resistant species. NORA research should focus on quantitative reconciliation of laboratory and epidemiology studies, and develop a counter "anti-hypothesis" generation research agenda for key exposure circumstances.
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BrooklynDodger(s) comment: The Dodger(s) picked up and use(s) the framework term "Houdini Risk Assessment" from this paper the Dodger(s) found. Many papers are published exploring the mechanisms of action of toxic chemicals. The contribution of this new knowledge to public health inteventions depends in part on whether the hazard has been identified in people, or is being extrapolated from laboratory studies in animal species.
Where "mechanistic" research arises from hazard identification in animal studies, and limited or no data from people, it is frequently advanced as a "morning after pill" to abort risk assessments. The absolute and binary conclusion that a mechanism is "not relevent to people" (peroxisome proliferation associated rodent liver tumors, kidney tumors in male rats, urinary bladder tumors associated with calculi) stops risk assessment at the hazard identification stage and ends the gestation of exposure response assessment.
A less pernicious use of mechanistic data might be estimating population variability in extrapolating to low dose risk. Were the human population widely variable in the biochemical parameter associated with potency, then a flatter population exposure response relationship would be expected, leading to higher unit risk estimates at lower doses where the human risk can't be directly observed. This line of argument would apply where hazard identification is based on higher dose human data.
Volume
9, Issue 5 September 2003 , pages 1129 - 1143
Does the Emperor Have Any Clothes: Using Mechanistic Information or Doing Houdini Risk Assessments?
Author: Mirer, Franklin E.1
Abstract: Risk assessment research rarely quells controversy. Mega-mouse, and mega-rat, experiments contradicted a threshold for carcinogenesis, yet thresholds are still argued. High to low dose continuity of response from cigarette smoking to environmental tobacco smoke, and from occupational asbestos exposure to take-home asbestos, contradict thresholds in people. Nevertheless, mechanistic hypotheses allege "Houdini Risk Assessments", which make risks disappear or allow industries to escape from protecting workers. Despite concerns for animal-to-human extrapolations, priority occupational exposures with sufficient or substantial evidence of carcinogenicity in people not addressed by new exposure limits include silica, sulfuric acid mist, chromates, diesel particulate matter, particulate matter generally, metalworking fluids, welding fume, and formaldehyde. "Houdini Risk Assessments" are exercises in "anti-hypothesis generation": ignore selected tumor sites and types; ignore data from people (as with formaldehyde and diesel); choose the most resistant species in laboratory tests; select biochemical parameters in which the most resistant species resembles people; assume a mechanism that gives threshold or steep exposure response for carcinogenic effect; and reduce estimated people risk by the parameter ratio to the most resistant species. NORA research should focus on quantitative reconciliation of laboratory and epidemiology studies, and develop a counter "anti-hypothesis" generation research agenda for key exposure circumstances.
>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: The Dodger(s) picked up and use(s) the framework term "Houdini Risk Assessment" from this paper the Dodger(s) found. Many papers are published exploring the mechanisms of action of toxic chemicals. The contribution of this new knowledge to public health inteventions depends in part on whether the hazard has been identified in people, or is being extrapolated from laboratory studies in animal species.
Where "mechanistic" research arises from hazard identification in animal studies, and limited or no data from people, it is frequently advanced as a "morning after pill" to abort risk assessments. The absolute and binary conclusion that a mechanism is "not relevent to people" (peroxisome proliferation associated rodent liver tumors, kidney tumors in male rats, urinary bladder tumors associated with calculi) stops risk assessment at the hazard identification stage and ends the gestation of exposure response assessment.
A less pernicious use of mechanistic data might be estimating population variability in extrapolating to low dose risk. Were the human population widely variable in the biochemical parameter associated with potency, then a flatter population exposure response relationship would be expected, leading to higher unit risk estimates at lower doses where the human risk can't be directly observed. This line of argument would apply where hazard identification is based on higher dose human data.
Wednesday, January 21, 2009
Silica Nanoparticles
Toxicology LettersVolume 184, Issue 1, 10 January 2009, Pages 18-25
Oxidative stress and pro-inflammatory responses induced by silica nanoparticles in vivo and in vitro
Eun-Jung Parka and Kwangsik Park, a,
aCollege of Pharmacy, Dongduk Women's University, 23-1 Wolgok-dong, Seongbuk-gu, Seoul 136-714, Republic of Korea
Received 27 June 2008;
Abstract
Oxidative stress and inflammatory responses induced by silica nanoparticles were evaluated both in mice and in RAW264.7 cell line. Single treatment of silica nanoparticles (50 mg/kg, i.p.) led to the activation of peritoneal macrophages, the increased blood level of IL-1β and TNF-α, and the increased level of nitric oxide released from the peritoneal macrophages. mRNA expressions of inflammation-related genes such as IL-1, IL-6, TNF-α, iNOS, and COX-2 were also elevated in the cultured peritoneal macrophages harvested from the treated mice. When the viability of splenocytes from the mice treated with silica nanoparticles (50 mg/kg, 100 mg/kg, and 250 mg/kg, i.p.) was measured, the viability of splenocytes was significantly decreased in the higher dose-treated groups (100 mg/kg, 200 mg/kg i.p.). However, cell proliferation without cytotoxicity was shown in group treated with relatively low dose of 50 mg/kg i.p. When leukocyte subtypes of mouse spleen were evaluated using flow cytometry analysis, it was found that the distributions of NK cells and T cells were increased to 184.8% and 115.1% of control, respectively, while that of B cells was decreased to 87.7%. To elucidate the pro-inflammatory mechanism of silica nanoparticles in vivo, in vitro study using RAW 264.7 cell line which is derived from mouse peritoneal macrophage was done. Treatment of silica nanoparticles to the cultured RAW264.7 cells led to the reactive oxygen species (ROS) generation with a decreased intracellular GSH. In accordance with ROS generation, silica nanoparticles increased the level of nitric oxide released from the cultured macrophage cell line. These results suggested that silica nanoparticles generate ROS and the generated ROS may trigger the pro-inflammatory responses both in vivo and in vitro.
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BrooklynDodger(s) comment(s): This is a bit of a hazard identification project: injected silica "nanoparticles" (nature unspecified in the abstract) cause inflammation and some immune system changes. This is toxic potential. It's disappointing not to have a comparison with non-nano silica particles to examine different potency of nano v non-nano. That would provide an aspect of exposure-response assessmnt.
Oxidative stress and pro-inflammatory responses induced by silica nanoparticles in vivo and in vitro
Eun-Jung Parka and Kwangsik Park, a,
aCollege of Pharmacy, Dongduk Women's University, 23-1 Wolgok-dong, Seongbuk-gu, Seoul 136-714, Republic of Korea
Received 27 June 2008;
Abstract
Oxidative stress and inflammatory responses induced by silica nanoparticles were evaluated both in mice and in RAW264.7 cell line. Single treatment of silica nanoparticles (50 mg/kg, i.p.) led to the activation of peritoneal macrophages, the increased blood level of IL-1β and TNF-α, and the increased level of nitric oxide released from the peritoneal macrophages. mRNA expressions of inflammation-related genes such as IL-1, IL-6, TNF-α, iNOS, and COX-2 were also elevated in the cultured peritoneal macrophages harvested from the treated mice. When the viability of splenocytes from the mice treated with silica nanoparticles (50 mg/kg, 100 mg/kg, and 250 mg/kg, i.p.) was measured, the viability of splenocytes was significantly decreased in the higher dose-treated groups (100 mg/kg, 200 mg/kg i.p.). However, cell proliferation without cytotoxicity was shown in group treated with relatively low dose of 50 mg/kg i.p. When leukocyte subtypes of mouse spleen were evaluated using flow cytometry analysis, it was found that the distributions of NK cells and T cells were increased to 184.8% and 115.1% of control, respectively, while that of B cells was decreased to 87.7%. To elucidate the pro-inflammatory mechanism of silica nanoparticles in vivo, in vitro study using RAW 264.7 cell line which is derived from mouse peritoneal macrophage was done. Treatment of silica nanoparticles to the cultured RAW264.7 cells led to the reactive oxygen species (ROS) generation with a decreased intracellular GSH. In accordance with ROS generation, silica nanoparticles increased the level of nitric oxide released from the cultured macrophage cell line. These results suggested that silica nanoparticles generate ROS and the generated ROS may trigger the pro-inflammatory responses both in vivo and in vitro.
>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment(s): This is a bit of a hazard identification project: injected silica "nanoparticles" (nature unspecified in the abstract) cause inflammation and some immune system changes. This is toxic potential. It's disappointing not to have a comparison with non-nano silica particles to examine different potency of nano v non-nano. That would provide an aspect of exposure-response assessmnt.
Tuesday, January 20, 2009
Not Asking the Right Questions About Injury Control in the Workplace
Applied ErgonomicsVolume 40, Issue 2, March 2009, Pages 185-193
The influence of individual and contextual work factors on workers’ compliance with health and safety routines
Steffen Torpa, , and Jens B. Grøgaardb
aFaculty of Health Sciences, Centre for Health Promotion in Settings, Vestfold University College, P.O. Box 2243, N-3103 Tønsberg, Norway
bFaculty of Social Sciences, Vestfold University College, Tønsberg, Norway
Abstract
This study investigated the relationships between workers’ compliance with health and safety (H&S) routines and instructions adopted in the company (dependent variable) and psychological demands, decision authority, social support, management support, unionization and H&S management system (independent variables). A cross-sectional questionnaire study was performed among 1051 workers and the managers of 102 small- and medium-sized motor vehicle repair garages. Multilevel modeling was performed to account for the hierarchical structure of the data. At the worker level, high compliance with H&S routines correlated significantly with both social support and H&S-related management support. At the garage level, mean management support and a well-developed H&S management system correlated significantly with high workers’ compliance. Changing both the individual and contextual factors in the work environment may thus increase workers’ participation in H&S activities.
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BrooklynDodger(s) comment: Probably the Dodger(s) should have read the full text to figure out what the safety "routines" were before complaining, but, whatever... The cause of injuries is contact with excessive energy - with hazards. The goal of worker participation in safety programs is identifying hazards and proposing abatements. using high levels of controls such as better equipment, guarding, or eliminating activities. These are garages, so the Dodger(s) suspect(s) the safety routines were mostly PPE.
The predominant injuries in workplaces of this type are musculoskeletal disorders from overexertion and repetitive motion.
What's the hypothesis for management "support" being necessary for workers to follow management's rules?
The influence of individual and contextual work factors on workers’ compliance with health and safety routines
Steffen Torpa, , and Jens B. Grøgaardb
aFaculty of Health Sciences, Centre for Health Promotion in Settings, Vestfold University College, P.O. Box 2243, N-3103 Tønsberg, Norway
bFaculty of Social Sciences, Vestfold University College, Tønsberg, Norway
Abstract
This study investigated the relationships between workers’ compliance with health and safety (H&S) routines and instructions adopted in the company (dependent variable) and psychological demands, decision authority, social support, management support, unionization and H&S management system (independent variables). A cross-sectional questionnaire study was performed among 1051 workers and the managers of 102 small- and medium-sized motor vehicle repair garages. Multilevel modeling was performed to account for the hierarchical structure of the data. At the worker level, high compliance with H&S routines correlated significantly with both social support and H&S-related management support. At the garage level, mean management support and a well-developed H&S management system correlated significantly with high workers’ compliance. Changing both the individual and contextual factors in the work environment may thus increase workers’ participation in H&S activities.
>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: Probably the Dodger(s) should have read the full text to figure out what the safety "routines" were before complaining, but, whatever... The cause of injuries is contact with excessive energy - with hazards. The goal of worker participation in safety programs is identifying hazards and proposing abatements. using high levels of controls such as better equipment, guarding, or eliminating activities. These are garages, so the Dodger(s) suspect(s) the safety routines were mostly PPE.
The predominant injuries in workplaces of this type are musculoskeletal disorders from overexertion and repetitive motion.
What's the hypothesis for management "support" being necessary for workers to follow management's rules?
Monday, January 19, 2009
Zinc Salt Instillation causes Cardiovascular Effects
Toxicology and Applied PharmacologyVolume 211, Issue 1, 15 February 2006, Pages 41-52
Cardiovascular and blood coagulative effects of pulmonary zinc exposure
Peter S. Gilmoura, Abraham Nyskab, Mette C. Schladweilerc, John K. McGeec, J. Grace Wallenbornd, Judy H. Richardsc and Urmila P. Kodavantic, ,
aCenter for Environmental Medicine, Asthma and Lung Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
bLaboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
cPulmonary Toxicology Branch, MD B143-01, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, ORD, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
dDepartment of Environmental Sciences and Engineering, UNC School of Public Health, Chapel Hill, NC 27599, USA
Abstract
Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Male Wistar Kyoto rats were instilled intratracheally with saline or zinc sulfate, 131 μg/kg (2 μmol/kg); the alterations were determined at 1, 4, 24, and 48 h postexposure. High-dose zinc enabled us to show changes in circulating levels of zinc above normal and induce significant pulmonary inflammation/injury such that cardiac impairments were likely. At 1–24 h postexposure, plasma levels of zinc increased to nearly 20% above the base line. Significant pulmonary inflammation and injury were determined by analysis of bronchoalveolar lavage fluid and histopathology in zinc-exposed rats at all time points. Starting at 4 h postexposure, pulmonary damage was accompanied by persistently increased gene expressions of tissue factor (TF) and plasminogen activator-inhibitor-1 (PAI-1), but not thrombomodulin (TM). Cardiac tissues demonstrated similar temporal increases in expressions of TF, PAI-1, and TM mRNA following pulmonary instillation of zinc. In contrast to extensive pulmonary edema and inflammation, only mild, and focal acute, myocardial lesions developed in a few zinc-exposed rats; no histological evidence showed increased deposition of fibrin or disappearance of troponin. At 24 and 48 h postexposure to zinc, increases occurred in levels of systemic fibrinogen and the activated partial thromboplastin time. These data suggest that cardiovascular blood coagulation impairments are likely following pulmonary zinc exposure and associated pulmonary injury and inflammation.
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BrooklynDodger(s) comment: This does appears to be a soluble zinc source. In occupational health practice, zinc and other metals are most associated with metal fume fever, which is usually discounted as a transient condition. Exposure response data on MFF are lacking in people, although the Dodger(s) believe MFF occurs at exposures less than the 5 mg/m3 PEL. An animal model for MFF would then enable titrating respiratory against the circulatory endpoints here. The doses in this study did not result in really large increases in circulating zinc levels.
Cardiovascular and blood coagulative effects of pulmonary zinc exposure
Peter S. Gilmoura, Abraham Nyskab, Mette C. Schladweilerc, John K. McGeec, J. Grace Wallenbornd, Judy H. Richardsc and Urmila P. Kodavantic, ,
aCenter for Environmental Medicine, Asthma and Lung Biology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
bLaboratory of Experimental Pathology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
cPulmonary Toxicology Branch, MD B143-01, Experimental Toxicology Division, National Health and Environmental Effects Research Laboratory, ORD, US Environmental Protection Agency, Research Triangle Park, NC 27711, USA
dDepartment of Environmental Sciences and Engineering, UNC School of Public Health, Chapel Hill, NC 27599, USA
Abstract
Cardiovascular damage induced by pulmonary exposure to environmental chemicals can result from direct action or, secondarily from pulmonary injury. We have developed a rat model of pulmonary exposure to zinc to demonstrate cardiac, coagulative, and fibrinolytic alterations. Male Wistar Kyoto rats were instilled intratracheally with saline or zinc sulfate, 131 μg/kg (2 μmol/kg); the alterations were determined at 1, 4, 24, and 48 h postexposure. High-dose zinc enabled us to show changes in circulating levels of zinc above normal and induce significant pulmonary inflammation/injury such that cardiac impairments were likely. At 1–24 h postexposure, plasma levels of zinc increased to nearly 20% above the base line. Significant pulmonary inflammation and injury were determined by analysis of bronchoalveolar lavage fluid and histopathology in zinc-exposed rats at all time points. Starting at 4 h postexposure, pulmonary damage was accompanied by persistently increased gene expressions of tissue factor (TF) and plasminogen activator-inhibitor-1 (PAI-1), but not thrombomodulin (TM). Cardiac tissues demonstrated similar temporal increases in expressions of TF, PAI-1, and TM mRNA following pulmonary instillation of zinc. In contrast to extensive pulmonary edema and inflammation, only mild, and focal acute, myocardial lesions developed in a few zinc-exposed rats; no histological evidence showed increased deposition of fibrin or disappearance of troponin. At 24 and 48 h postexposure to zinc, increases occurred in levels of systemic fibrinogen and the activated partial thromboplastin time. These data suggest that cardiovascular blood coagulation impairments are likely following pulmonary zinc exposure and associated pulmonary injury and inflammation.
>>>>>>>>>>>>
BrooklynDodger(s) comment: This does appears to be a soluble zinc source. In occupational health practice, zinc and other metals are most associated with metal fume fever, which is usually discounted as a transient condition. Exposure response data on MFF are lacking in people, although the Dodger(s) believe MFF occurs at exposures less than the 5 mg/m3 PEL. An animal model for MFF would then enable titrating respiratory against the circulatory endpoints here. The doses in this study did not result in really large increases in circulating zinc levels.
Sunday, January 18, 2009
Formaldehyde Causes Genotoxic Effects at Exposure Levels about Half the OSHA Standard
Toxicology Volume 252, Issues 1-3, 30 October 2008, Pages 40-48
Genotoxic damage in pathology anatomy laboratory workers exposed to formaldehyde
Solange Costaa, b, , , , Patrícia Coelhoa, Carla Costaa, Susana Silvaa, Olga Mayana, Luís Silva Santosc, d, Jorge Gasparc and João Paulo Teixeiraa
aNational Institute of Health, Environmental Health Department, Praça Coronel Pacheco 15, 4050-453 Porto, Portugal
bEscola Superior de Biotecnologia da Universidade Católica Portuguesa, Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal
cFaculty of Medical Sciences UNL, Department of Genetics, Rua da Junqueira 96, 1349-008 Lisboa, Portugal
dCentro Regional das Beiras, Universidade Católica Portuguesa, Estrada da Circunvalação, 3504-505 Viseu, Portugal
Solange Costaa, b, , , , Patrícia Coelhoa, Carla Costaa, Susana Silvaa, Olga Mayana, Luís Silva Santosc, d, Jorge Gasparc and João Paulo Teixeiraa
aNational Institute of Health, Environmental Health Department, Praça Coronel Pacheco 15, 4050-453 Porto, Portugal
bEscola Superior de Biotecnologia da Universidade Católica Portuguesa, Rua Dr António Bernardino de Almeida, 4200-072 Porto, Portugal
cFaculty of Medical Sciences UNL, Department of Genetics, Rua da Junqueira 96, 1349-008 Lisboa, Portugal
dCentro Regional das Beiras, Universidade Católica Portuguesa, Estrada da Circunvalação, 3504-505 Viseu, Portugal
Abstract
Formaldehyde (FA) is a chemical traditionally used in pathology and anatomy laboratories as a tissue preservative. Several epidemiological studies of occupational exposure to FA have indicated an increased risk of nasopharyngeal cancers in industrial workers, embalmers and pathology anatomists. There is also a clear evidence of nasal squamous cell carcinomas from inhalation studies in the rat. The postulated mode of action for nasal tumours in rats was considered biologically plausible and considered likely to be relevant to humans. Based on the available data IARC, the International Agency for Research on Cancer, has recently classified FA as a human carcinogen. Although the in vitro genotoxic as well as the in vivo carcinogenic potentials of FA are well documented in mammalian cells and in rodents, evidence for genotoxic effects and carcinogenic properties in humans is insufficient and conflicting thus remains to be more documented. To evaluate the genetic effects of long-term occupational exposure to FA a group of 30 Pathological Anatomy laboratory workers was tested for a variety of biological endpoints, cytogenetic tests (micronuclei, MN; sister chromatid exchange, SCE) and comet assay. The level of exposure to FA was evaluated near the breathing zone of workers, time weighted average of exposure was calculated for each subject. The association between the biomarkers and polymorphic genes of xenobiotic metabolising and DNA repair enzymes was also assessed. The mean level of exposure was 0.44 ± 0.08 ppm (0.04–1.58 ppm). MN frequency was significantly higher (p = 0.003) in the exposed subjects (5.47 ± 0.76) when compared with controls (3.27 ± 0.69). SCE mean value was significantly higher (p < r =" 0.384," p =" 0.001)" r =" 0.333," p =" 0.005)> Regarding the genetic polymorphisms studied, no significant effect was found on the genotoxic endpoints. The results of the present biomonitoring study emphasize the need to develop safety programs.
Formaldehyde (FA) is a chemical traditionally used in pathology and anatomy laboratories as a tissue preservative. Several epidemiological studies of occupational exposure to FA have indicated an increased risk of nasopharyngeal cancers in industrial workers, embalmers and pathology anatomists. There is also a clear evidence of nasal squamous cell carcinomas from inhalation studies in the rat. The postulated mode of action for nasal tumours in rats was considered biologically plausible and considered likely to be relevant to humans. Based on the available data IARC, the International Agency for Research on Cancer, has recently classified FA as a human carcinogen. Although the in vitro genotoxic as well as the in vivo carcinogenic potentials of FA are well documented in mammalian cells and in rodents, evidence for genotoxic effects and carcinogenic properties in humans is insufficient and conflicting thus remains to be more documented. To evaluate the genetic effects of long-term occupational exposure to FA a group of 30 Pathological Anatomy laboratory workers was tested for a variety of biological endpoints, cytogenetic tests (micronuclei, MN; sister chromatid exchange, SCE) and comet assay. The level of exposure to FA was evaluated near the breathing zone of workers, time weighted average of exposure was calculated for each subject. The association between the biomarkers and polymorphic genes of xenobiotic metabolising and DNA repair enzymes was also assessed. The mean level of exposure was 0.44 ± 0.08 ppm (0.04–1.58 ppm). MN frequency was significantly higher (p = 0.003) in the exposed subjects (5.47 ± 0.76) when compared with controls (3.27 ± 0.69). SCE mean value was significantly higher (p < r =" 0.384," p =" 0.001)" r =" 0.333," p =" 0.005)> Regarding the genetic polymorphisms studied, no significant effect was found on the genotoxic endpoints. The results of the present biomonitoring study emphasize the need to develop safety programs.
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BrooklynDodger(s) comments: The Dodger(s) troll Toxicology and other laboratory journals for the few papers which involve a chemical with recognizable occupational or environmental exposures. It took several issues to find something. This suggest maybe most toxicology research generating peer reviewed literature is not relevant to public health.
Expansion of public health research beyond the United States is important to expanding our knowledge base. The EU, China and India may have to carry the field until US science recovers from the not yet over Bush Administration. This report is from Portugal.
The exposures averaged 0.44 ppm. This was an effect level for three types of genetic damage. Therefore, a NOAEL for genotoxicity was not established. A PEL to eliminate significant risk should be 10 to 100 fold below. The fact of damage in circulating cells also contradicts the industry claim that formaldehyde is not absorbed into somatic tissues, an argument against the observed association between formaldehyde exposures and leukemia.
Saturday, January 17, 2009
Wood Dust - Another high exposure carcinogen not regulated hardly by anyone.
Mutagenesis 2009 24(1):59-65; doi:10.1093/mutage/gen053
Genetic damage in wood dust-exposed workers
P. V. Rekhadevi, M. Mahboob, M. F. Rahman and Paramjit Grover*
Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad 500 607, Andhra Pradesh, India
Exposure to wood dust is common in carpentry workshops. Wood dust is known to be a human carcinogen, with a very high relative risk of adenocarcinoma of the nasal cavities and paranasal sinuses. The goal of this investigation was to conduct genotoxicity monitoring of carpenters involved in wooden furniture industry in order to test possible wood dust-induced genotoxic effects due to occupational exposure. The level of genetic damage was determined by comet, micronucleus and chromosomal aberration (CA) assays in peripheral blood lymphocytes (PBL) of 60 carpentry workers. In addition, the micronucleus test in buccal epithelial cells was carried out in the same subjects. Total antioxidant enzyme activities were measured by the indices: superoxide dismutase, glutathione peroxidase and catalase. A group of 60 non-exposed subjects matched by age, smoking and alcohol consumption habits were chosen as controls. The effect of age, smoking, alcohol consumption and duration of exposure was also analysed in the subjects of the present study. The results showed a statistically significant increase in mean DNA damage by comet assay, micronuclei frequency in buccal cells as well as PBL and frequency of CA in the exposed workers when compared to controls
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BrooklynDodger(s) comment: The two known human carcinogens with broad exposure most ignored by public health agencies are wood dust and sulfuric acid.
This study found genetic damage, including damage in circulating lymphocytes, indicating some penetration into the body. Unfortunately, there were no exposure levels cited.
Genetic damage in wood dust-exposed workers
P. V. Rekhadevi, M. Mahboob, M. F. Rahman and Paramjit Grover*
Toxicology Unit, Biology Division, Indian Institute of Chemical Technology, Hyderabad 500 607, Andhra Pradesh, India
Exposure to wood dust is common in carpentry workshops. Wood dust is known to be a human carcinogen, with a very high relative risk of adenocarcinoma of the nasal cavities and paranasal sinuses. The goal of this investigation was to conduct genotoxicity monitoring of carpenters involved in wooden furniture industry in order to test possible wood dust-induced genotoxic effects due to occupational exposure. The level of genetic damage was determined by comet, micronucleus and chromosomal aberration (CA) assays in peripheral blood lymphocytes (PBL) of 60 carpentry workers. In addition, the micronucleus test in buccal epithelial cells was carried out in the same subjects. Total antioxidant enzyme activities were measured by the indices: superoxide dismutase, glutathione peroxidase and catalase. A group of 60 non-exposed subjects matched by age, smoking and alcohol consumption habits were chosen as controls. The effect of age, smoking, alcohol consumption and duration of exposure was also analysed in the subjects of the present study. The results showed a statistically significant increase in mean DNA damage by comet assay, micronuclei frequency in buccal cells as well as PBL and frequency of CA in the exposed workers when compared to controls
>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: The two known human carcinogens with broad exposure most ignored by public health agencies are wood dust and sulfuric acid.
This study found genetic damage, including damage in circulating lymphocytes, indicating some penetration into the body. Unfortunately, there were no exposure levels cited.
Friday, January 16, 2009
Formaldehyde exposure limits - Take Your Pick
http://www.propublica.org/article/formaldehyde-found-in-houses-provided-for-katrina-victims-in-mississippi-12
Formaldehyde Found in Houses Provided for Katrina Victims in Mississippi...
"Earlier this month, a MEMA [?Mississippi Emergency Management Agency?] spokesman told the Biloxi Sun Herald that it still hadn’t conducted the promised testing. But documents obtained by the Sierra Club show that MEMA had in fact tested some of the cottages in April and found formaldehyde at levels between .046 parts per million and .116 parts per million.
The National Institute for Occupational Safety and Health recommends that workers should not be exposed to an average of .016 parts per million for more than 10 hours without wearing a respirator. FEMA adopted that standard for its trailers in April 2008, after a congressional investigation revealed that the agency avoided testing trailers for formaldehyde because of concerns about litigation.
In defense of MEMA, its executive director, Mike Womack, said the agency’s tests were designed only to determine whether factors like temperature, humidity, or the amount of time a unit was closed after shipment affected formaldehyde levels. He said the federal government has so many conflicting formaldehyde standards that it was hard for MEMA to determine which one to follow, especially since none of the standards apply specifically to formaldehyde levels inside homes."
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BrooklynDodger(s) comment: The issue of acceptible exposure levels for formaldehyde seems to surface only when a public agency is responsible for new construction or possibly newly insulated residences. This news story has moved from trailers to cottages. The Dodger(s) have previously noted that EPA appears to be working on a new risk assessment for formaldehyde, in response to a Section 21 TSCA petition by NRDC and others.
In the interest of a simple blog post, the Dodger(s) now supply the range of exposure limits:
The OSHA limits are a PEL of 0.75 ppm TWA, 2 ppm STEL, an action level which triggers monitoring and active medical surveillance of 0.5 ppm. In addition, exposures over 0.1 ppm and symptoms trigger employee training and an obligation for medical surveillance after complaints. In the formaldehyde standard, medical surveillance includes medical removal protection and multiple physician review.
The ACGIH® TLV for formaldehyde is 0.3 ppm ceiling limit, nearly tenfold more protective than the OSHA STEL.
The NIOSH REL for formaldehyde is 0.016 ppm for a 10-hour TWA and 0.1 ppm for 15 minutes.
The EPA Integrated Risk Information System (IRIS) does not include a “reference concentration” for formaldehyde, although it predicts a 1/10,000 risk of cancer at 7 ppb (likely for 24-hour exposure over a lifetime) based on laboratory studies.
Finally, ATSDR publishes several “minimum risk levels”: 0.04 ppm for acute exposure (1–14 days), 0.03 ppm for intermediate exposure (14–364 days) and 0.008 ppm for chronic exposure (365 days and longer). See www.atsdr.cdc.gov/mrls/index.html for more information.
Formaldehyde Found in Houses Provided for Katrina Victims in Mississippi...
"Earlier this month, a MEMA [?Mississippi Emergency Management Agency?] spokesman told the Biloxi Sun Herald that it still hadn’t conducted the promised testing. But documents obtained by the Sierra Club show that MEMA had in fact tested some of the cottages in April and found formaldehyde at levels between .046 parts per million and .116 parts per million.
The National Institute for Occupational Safety and Health recommends that workers should not be exposed to an average of .016 parts per million for more than 10 hours without wearing a respirator. FEMA adopted that standard for its trailers in April 2008, after a congressional investigation revealed that the agency avoided testing trailers for formaldehyde because of concerns about litigation.
In defense of MEMA, its executive director, Mike Womack, said the agency’s tests were designed only to determine whether factors like temperature, humidity, or the amount of time a unit was closed after shipment affected formaldehyde levels. He said the federal government has so many conflicting formaldehyde standards that it was hard for MEMA to determine which one to follow, especially since none of the standards apply specifically to formaldehyde levels inside homes."
>>>>>>>>>>>>>
BrooklynDodger(s) comment: The issue of acceptible exposure levels for formaldehyde seems to surface only when a public agency is responsible for new construction or possibly newly insulated residences. This news story has moved from trailers to cottages. The Dodger(s) have previously noted that EPA appears to be working on a new risk assessment for formaldehyde, in response to a Section 21 TSCA petition by NRDC and others.
In the interest of a simple blog post, the Dodger(s) now supply the range of exposure limits:
The OSHA limits are a PEL of 0.75 ppm TWA, 2 ppm STEL, an action level which triggers monitoring and active medical surveillance of 0.5 ppm. In addition, exposures over 0.1 ppm and symptoms trigger employee training and an obligation for medical surveillance after complaints. In the formaldehyde standard, medical surveillance includes medical removal protection and multiple physician review.
The ACGIH® TLV for formaldehyde is 0.3 ppm ceiling limit, nearly tenfold more protective than the OSHA STEL.
The NIOSH REL for formaldehyde is 0.016 ppm for a 10-hour TWA and 0.1 ppm for 15 minutes.
The EPA Integrated Risk Information System (IRIS) does not include a “reference concentration” for formaldehyde, although it predicts a 1/10,000 risk of cancer at 7 ppb (likely for 24-hour exposure over a lifetime) based on laboratory studies.
Finally, ATSDR publishes several “minimum risk levels”: 0.04 ppm for acute exposure (1–14 days), 0.03 ppm for intermediate exposure (14–364 days) and 0.008 ppm for chronic exposure (365 days and longer). See www.atsdr.cdc.gov/mrls/index.html for more information.
Thursday, January 15, 2009
OSHA Injury Rate - Figures Don't Lie, But ...
Occupational and Environmental Medicine 2007;64:454-460The impact of OSHA recordkeeping regulation changes on occupational injury and illness trends in the US: a time-series analysisLee S Friedman, Linda Forst
University of Illinois at Chicago, School of Public Health, Division of Environmental and Occupational Health Sciences, Chicago, Illinois, USA
Correspondence to:Correspondence to: Dr L S Friedman University of Illinois at Chicago, 2121W Taylor St, Chicago, IL 60612, USA; lfriedman@tspri.org
Methods: SOII data available from the Bureau of Labor Statistics for years 1992–2003 were collected. The authors assessed time series data using join-point regression models.
Results: Before the first major recordkeeping change in 1995, injuries and illnesses declined annually by 0.5%. In the period 1995–2000 the slope declined by 3.1% annually (95% CI –3.7% to –2.5%), followed by another more precipitous decline occurring in 2001–2003 (–8.3%; 95% CI –10.0% to –6.6%). When stratifying the data, the authors continued to observe significant changes occurring in 1995 and 2001.
Conclusions: The substantial declines in the number of injuries and illnesses correspond directly with changes in OSHA recordkeeping rules. Changes in employment, productivity, OSHA enforcement activity and sampling error do not explain the large decline. Based on the baseline slope (join-point regression analysis, 1992–4), the authors expected a decline of 407 964 injuries and illnesses during the period of follow-up if no intervention occurred; they actually observed a decline of 2.4 million injuries and illnesses of which 2 million or 83% of the decline can be attributed to the change in the OSHA recordkeeping rules."
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BrooklynDodger(s) comment:
At the national level, the Administration mirrors the facility level tactic of claiming safety and progress towards more safety by referring to the incidence rate. At the facility level, the management safety activity, which gets rated by its rate, keeps the numbers. At the national level, BLS collects the data, but OSHA enforces or doesn't enforce the rules for recording. Audits of injury data are as reliable as audits of mortgage securities.
Colleagues at UIC have served us well by conducting an academic investigation of the plausibility of reductions observed by the Bush Administration. This is one of several peer reviewed publications in the area.
This investigation used the data as provided, and assumes that facilities are following the rules. It doesn't take into account systematic efforts to discourage reporting, and suppress recording beyond what's permitted by the rules.
Determining the injury rate by census of employer recorded data is backward and wasteful. The new administration should launch a population survey, similar to the methods for measuring unemployment.
Wednesday, January 14, 2009
Yet Another Failed Chemoprevention Trial
Vitamins E and C in the Prevention of Prostate and Total Cancer in Men : The Physicians' Health Study II Randomized Controlled Trial
J. Michael Gaziano, MD, MPH; Robert J. Glynn, ScD; William G. Christen, ScD; Tobias Kurth, MD, ScD; Charlene Belanger, MA; Jean MacFadyen, BA; Vadim Bubes, PhD; JoAnn E. Manson, MD, DrPH; Howard D. Sesso, ScD, MPH; Julie E. Buring, ScD
JAMA. 2009;301(1):52-62.
Context Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer.
Objective To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men.
Design, Setting, and Participants The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14 641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled.
Intervention Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily.
Main Outcome Measures Prostate and total cancer.
Results During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk.
Conclusions In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men.
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BrooklynDodger(s) comment: The Dodger(s) continue to kick sand in the face of chemoprevention (silica exposure?) At least this study only cost us for 16,000 subjects, not 35,000. The abstract yields a heuristic - a bit more than 10% of these 50 year old men got cancer over the next 8 years from enrollment.
J. Michael Gaziano, MD, MPH; Robert J. Glynn, ScD; William G. Christen, ScD; Tobias Kurth, MD, ScD; Charlene Belanger, MA; Jean MacFadyen, BA; Vadim Bubes, PhD; JoAnn E. Manson, MD, DrPH; Howard D. Sesso, ScD, MPH; Julie E. Buring, ScD
JAMA. 2009;301(1):52-62.
Context Many individuals take vitamins in the hopes of preventing chronic diseases such as cancer, and vitamins E and C are among the most common individual supplements. A large-scale randomized trial suggested that vitamin E may reduce risk of prostate cancer; however, few trials have been powered to address this relationship. No previous trial in men at usual risk has examined vitamin C alone in the prevention of cancer.
Objective To evaluate whether long-term vitamin E or C supplementation decreases risk of prostate and total cancer events among men.
Design, Setting, and Participants The Physicians' Health Study II is a randomized, double-blind, placebo-controlled factorial trial of vitamins E and C that began in 1997 and continued until its scheduled completion on August 31, 2007. A total of 14 641 male physicians in the United States initially aged 50 years or older, including 1307 men with a history of prior cancer at randomization, were enrolled.
Intervention Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily.
Main Outcome Measures Prostate and total cancer.
Results During a mean follow-up of 8.0 years, there were 1008 confirmed incident cases of prostate cancer and 1943 total cancers. Compared with placebo, vitamin E had no effect on the incidence of prostate cancer (active and placebo vitamin E groups, 9.1 and 9.5 events per 1000 person-years; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.85-1.09; P = .58) or total cancer (active and placebo vitamin E groups, 17.8 and 17.3 cases per 1000 person-years; HR, 1.04; 95% CI, 0.95-1.13; P = .41). There was also no significant effect of vitamin C on total cancer (active and placebo vitamin C groups, 17.6 and 17.5 events per 1000 person-years; HR, 1.01; 95% CI, 0.92-1.10; P = .86) or prostate cancer (active and placebo vitamin C groups, 9.4 and 9.2 cases per 1000 person-years; HR, 1.02; 95% CI, 0.90-1.15; P = .80). Neither vitamin E nor vitamin C had a significant effect on colorectal, lung, or other site-specific cancers. Adjustment for adherence and exclusion of the first 4 or 6 years of follow-up did not alter the results. Stratification by various cancer risk factors demonstrated no significant modification of the effect of vitamin E on prostate cancer risk or either agent on total cancer risk.
Conclusions In this large, long-term trial of male physicians, neither vitamin E nor C supplementation reduced the risk of prostate or total cancer. These data provide no support for the use of these supplements for the prevention of cancer in middle-aged and older men.
>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: The Dodger(s) continue to kick sand in the face of chemoprevention (silica exposure?) At least this study only cost us for 16,000 subjects, not 35,000. The abstract yields a heuristic - a bit more than 10% of these 50 year old men got cancer over the next 8 years from enrollment.
Tuesday, January 13, 2009
Flushing Your Money on Anti-oxidants - Another Chemoprevention Trial Bites the Dust
Effect of Selenium and Vitamin E on Risk of Prostate Cancer and Other Cancers The Selenium and Vitamin E Cancer Prevention Trial (SELECT)
Scott M. Lippman, MD; Eric A. Klein, MD; Phyllis J. Goodman, MS; M. Scott Lucia, MD; Ian M. Thompson, MD; Leslie G. Ford, MD; Howard L. Parnes, MD; Lori M. Minasian, MD; J. Michael Gaziano, MD, MPH; Jo Ann Hartline, MPH; J. Kellogg Parsons, MD, MHS; James D. Bearden III, MD; E. David Crawford, MD; Gary E. Goodman, MD; Jaime Claudio, MD; Eric Winquist, MD, MSc; Elise D. Cook, MD; Daniel D. Karp, MD; Philip Walther, MD; Michael M. Lieber, MD; Alan R. Kristal, DrPH; Amy K. Darke, MS; Kathryn B. Arnold, MS; Patricia A. Ganz, MD; Regina M. Santella, PhD; Demetrius Albanes, MD; Philip R. Taylor, MD, ScD; Jeffrey L. Probstfield, MD; T. J. Jagpal, CCRP; John J. Crowley, PhD; Frank L. Meyskens Jr, MD; Laurence H. Baker, DO; Charles A. Coltman Jr, MD
JAMA. 2009;301(1):39-51.
Context Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer.
Objective To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men.
Design, Setting, and Participants A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35 533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer.
Interventions Oral selenium (200 µg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac--tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.
Main Outcome Measures Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer.
Results As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group.
Conclusion Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.
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BrooklynDodger(s) comment: Many would hope that cancer could be prevented by eating your vegetables or taking stuff from the health food store. Lots easier than preventing exposure to carcinogens. There's a loose hypothesis that anti-oxidants prevent cancer, since some oxidants cause cancer.
So, somebody funded a 35,000 person cohort. Imagine the industrial cohorts which could have been studied to that!!
Those continuing proponents of chemoprevention could argue that the observation period was only 5 years, so the effect would only be on pre-enrollment tumors. If vitamin E is good for you, it would also be good for tumor cells.
The Dodger(s) continue to hope in vain for funding on true prevention, which would identify chemical risks. On the other hand, it's good to see some interest in prostate cancer, which kills as many as breast cancer, but has no lobby.
[By the way, "flushing" in the title is meant to evoke some connection to urinary problems associated with BPH]
Scott M. Lippman, MD; Eric A. Klein, MD; Phyllis J. Goodman, MS; M. Scott Lucia, MD; Ian M. Thompson, MD; Leslie G. Ford, MD; Howard L. Parnes, MD; Lori M. Minasian, MD; J. Michael Gaziano, MD, MPH; Jo Ann Hartline, MPH; J. Kellogg Parsons, MD, MHS; James D. Bearden III, MD; E. David Crawford, MD; Gary E. Goodman, MD; Jaime Claudio, MD; Eric Winquist, MD, MSc; Elise D. Cook, MD; Daniel D. Karp, MD; Philip Walther, MD; Michael M. Lieber, MD; Alan R. Kristal, DrPH; Amy K. Darke, MS; Kathryn B. Arnold, MS; Patricia A. Ganz, MD; Regina M. Santella, PhD; Demetrius Albanes, MD; Philip R. Taylor, MD, ScD; Jeffrey L. Probstfield, MD; T. J. Jagpal, CCRP; John J. Crowley, PhD; Frank L. Meyskens Jr, MD; Laurence H. Baker, DO; Charles A. Coltman Jr, MD
JAMA. 2009;301(1):39-51.
Context Secondary analyses of 2 randomized controlled trials and supportive epidemiologic and preclinical data indicated the potential of selenium and vitamin E for preventing prostate cancer.
Objective To determine whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in relatively healthy men.
Design, Setting, and Participants A randomized, placebo-controlled trial (Selenium and Vitamin E Cancer Prevention Trial [SELECT]) of 35 533 men from 427 participating sites in the United States, Canada, and Puerto Rico randomly assigned to 4 groups (selenium, vitamin E, selenium + vitamin E, and placebo) in a double-blind fashion between August 22, 2001, and June 24, 2004. Baseline eligibility included age 50 years or older (African American men) or 55 years or older (all other men), a serum prostate-specific antigen level of 4 ng/mL or less, and a digital rectal examination not suspicious for prostate cancer.
Interventions Oral selenium (200 µg/d from L-selenomethionine) and matched vitamin E placebo, vitamin E (400 IU/d of all rac--tocopheryl acetate) and matched selenium placebo, selenium + vitamin E, or placebo + placebo for a planned follow-up of minimum of 7 years and a maximum of 12 years.
Main Outcome Measures Prostate cancer and prespecified secondary outcomes, including lung, colorectal, and overall primary cancer.
Results As of October 23, 2008, median overall follow-up was 5.46 years (range, 4.17-7.33 years). Hazard ratios (99% confidence intervals [CIs]) for prostate cancer were 1.13 (99% CI, 0.95-1.35; n = 473) for vitamin E, 1.04 (99% CI, 0.87-1.24; n = 432) for selenium, and 1.05 (99% CI, 0.88-1.25; n = 437) for selenium + vitamin E vs 1.00 (n = 416) for placebo. There were no significant differences (all P>.15) in any other prespecified cancer end points. There were statistically nonsignificant increased risks of prostate cancer in the vitamin E group (P = .06) and type 2 diabetes mellitus in the selenium group (relative risk, 1.07; 99% CI, 0.94-1.22; P = .16) but not in the selenium + vitamin E group.
Conclusion Selenium or vitamin E, alone or in combination at the doses and formulations used, did not prevent prostate cancer in this population of relatively healthy men.
>>>>>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: Many would hope that cancer could be prevented by eating your vegetables or taking stuff from the health food store. Lots easier than preventing exposure to carcinogens. There's a loose hypothesis that anti-oxidants prevent cancer, since some oxidants cause cancer.
So, somebody funded a 35,000 person cohort. Imagine the industrial cohorts which could have been studied to that!!
Those continuing proponents of chemoprevention could argue that the observation period was only 5 years, so the effect would only be on pre-enrollment tumors. If vitamin E is good for you, it would also be good for tumor cells.
The Dodger(s) continue to hope in vain for funding on true prevention, which would identify chemical risks. On the other hand, it's good to see some interest in prostate cancer, which kills as many as breast cancer, but has no lobby.
[By the way, "flushing" in the title is meant to evoke some connection to urinary problems associated with BPH]
Monday, January 12, 2009
Real Primary Prevention - Obesity Causes Disease, but What Causes Obesity?
Am J Prev Med Volume 36, Issue 1, Pages 1-8 (January 2009)
Posttraumatic Stress Disorder and Obesity: Evidence for a Risk Association
Axel Perkonigg, PhDac, Toshimi Owashi, MDcd, Murray B. Stein, MD, MPHe, Clemens Kirschbaum, PhDb, Hans-Ulrich Wittchen, PhDac
published online 03 November 2008.
"Background
There is evidence from cross-sectional studies that posttraumatic stress disorder (PTSD) may be associated with obesity. The aim of this study was to examine prospective longitudinal associations between PTSD and obesity in a community sample.
Methods
A prospective, longitudinal, epidemiologic study with a representative community sample of adolescents and young adults (N=3021, aged 14–24 years at baseline) was conducted in Munich, Germany. Participants were assessed four times between 1995 and 2005 with the Munich-Composite International Diagnostic Interview. Associations between obesity (BMI ≥30) and DSM-IV PTSD were evaluated in 2007, using cross-sectional and prospective data during young adulthood.
Results
The cumulative lifetime incidence of obesity in the sample at 10-year follow-up during young adulthood was 4.3% (women, 4.6%; men, 4.0%). Among women but not among men, obesity was associated with a lifetime history of PTSD (OR=3.8; 95% CI=1.4, 10.7) in the cross-sectional analyses. Prospective longitudinal analyses from 4-year follow-up to 10-year follow-up confirmed that obesity was predicted by antecedent subthreshold and full PTSD (OR=3.0; 95% CI=1.3, 7.0) among women but not among men. There were no associations between other mental disorders and obesity in the prospective analyses.
Conclusions
The findings indicate a possible causal pathway for the onset of obesity in females with PTSD symptoms. These findings need replication with regard to the pathophysiologic and behavioral mechanisms underlying this relationship."
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BrooklynDodger(s) comment: This publication adds to the framework asserting that "pain," broadly defined, causes health risk behavior, by this mechanism causing adverse intermediate conditions (obesity) leading to adverse outcomes. This publication finds an association between PTSD and later obesity among women but not men. The absence of an association among men - who suffered an equivalent incidence of obesity - might be explained by the greater prevalence of other stressors among men. This is clearly culturally defined by Munich.
The literature about obsesity and adverse effects is suffused with the odor of moral panic and victim blaming. Another post sometime will address this.
Posttraumatic Stress Disorder and Obesity: Evidence for a Risk Association
Axel Perkonigg, PhDac, Toshimi Owashi, MDcd, Murray B. Stein, MD, MPHe, Clemens Kirschbaum, PhDb, Hans-Ulrich Wittchen, PhDac
published online 03 November 2008.
"Background
There is evidence from cross-sectional studies that posttraumatic stress disorder (PTSD) may be associated with obesity. The aim of this study was to examine prospective longitudinal associations between PTSD and obesity in a community sample.
Methods
A prospective, longitudinal, epidemiologic study with a representative community sample of adolescents and young adults (N=3021, aged 14–24 years at baseline) was conducted in Munich, Germany. Participants were assessed four times between 1995 and 2005 with the Munich-Composite International Diagnostic Interview. Associations between obesity (BMI ≥30) and DSM-IV PTSD were evaluated in 2007, using cross-sectional and prospective data during young adulthood.
Results
The cumulative lifetime incidence of obesity in the sample at 10-year follow-up during young adulthood was 4.3% (women, 4.6%; men, 4.0%). Among women but not among men, obesity was associated with a lifetime history of PTSD (OR=3.8; 95% CI=1.4, 10.7) in the cross-sectional analyses. Prospective longitudinal analyses from 4-year follow-up to 10-year follow-up confirmed that obesity was predicted by antecedent subthreshold and full PTSD (OR=3.0; 95% CI=1.3, 7.0) among women but not among men. There were no associations between other mental disorders and obesity in the prospective analyses.
Conclusions
The findings indicate a possible causal pathway for the onset of obesity in females with PTSD symptoms. These findings need replication with regard to the pathophysiologic and behavioral mechanisms underlying this relationship."
>>>>>>>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comment: This publication adds to the framework asserting that "pain," broadly defined, causes health risk behavior, by this mechanism causing adverse intermediate conditions (obesity) leading to adverse outcomes. This publication finds an association between PTSD and later obesity among women but not men. The absence of an association among men - who suffered an equivalent incidence of obesity - might be explained by the greater prevalence of other stressors among men. This is clearly culturally defined by Munich.
The literature about obsesity and adverse effects is suffused with the odor of moral panic and victim blaming. Another post sometime will address this.
Sunday, January 11, 2009
Structure Activity Relationships: No one predicted Diacetyl Toxicity; What does Disacetyl Predict?
Bioorg Med Chem. 2003 Mar 20;11(6):853-62.
The role of dicarbonyl compounds in non-enzymatic crosslinking: a structure-activity study.
Meade SJ, Miller AG, Gerrard JA. Department of Plant and Microbial Sciences, University of Canterbury, Private Bag 4800, Christchurch, New Zealand.
The Maillard reaction is a complex network of reactions that has been shown to result in the non-enzymatic crosslinking of proteins. Recent attention has focussed on the role of alpha-dicarbonyl compounds as important in vivo contributors to protein crosslinking but, despite extensive research, the molecular mechanisms of the crosslinking reaction remain open to conjecture. In particular, no relationship between the structure of the carbonyl-containing compounds and their activity as crosslinking agents has been established. In an effort to elucidate a structure-reactivity relationship, a wide range of dicarbonyl compounds, including linear, cyclic, di-aldehyde and di-ketone compounds, were reacted with the model protein ribonuclease A and their crosslinking activity assessed. Methylglyoxal and glutaraldehyde were found to be the most efficient crosslinkers, whilst closely related molecules effected crosslinking at a much lower rate. Cyclopentan-1,2-dione was also shown to be a reactive crosslinking agent. The efficiency of methylglyoxal and glutaraldehyde at crosslinking is thought to be related to their ability to form stable heterocyclic compounds that are the basis of protein crosslinks. The reasons for the striking reactivity of these two compounds, compared to closely related structures is explained by subtle balances between competing pathways in a complex reaction network.
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BrooklynDodger(s) comments: Most toxicology textbooks and writings about risk assessment mention "structure activity relationships" as a method of hazard identification. There is some funding for computational toxicology. The Dodger(s) think(s) this is wasted space and money in occupational, environmental (including food) toxicology. It reflects the pharmacology roots of many toxicologists; pharmacologists who use this for suggesting "me too" drugs. Some of the key agents identified in recent years demonstrate the failure of this approach to spur research before the fact. Maybe the best known is n-hexane, methyl-n-butylketone (2-hexanone), 2,5-hexadione sequence causing peripheral neuropathy. The Dodger(s) haven't seen a convincing explanation of why n-heptane is not known to cause the peripheral neuropathy demonstrated in the laboratory after people got sick. Butadiene, chloroprene and isoprene (1,3 dienes) are carcinogenic by inhalation, especially butadiene with great potency.
Which brings us to popcorn lung. When diacetyl (2,3-butadiONE) was first proposed as a cause of popcorn lung, the Dodger(s) were skeptical. To a toxicologist, it didn't look like much, it was GRAS, and it was even in beer. So the issue is whether the toxicity of diacetyl could be anticipated from structure activity. The alpha, beta dione structure could suggest some kind of electrocyclic reaction, but it turns out that a much simpler effect was known, the Maillard Reaction, well known in the food chemistry circles. The Dodger(s) didn't find any special reference to diacetyl in the publication abstracted above.
The Dodger(s) would propose that chemicals containing the 1,3-diene or the 2,4-dione moiety be considered toxic until proven innocent. And that future computational toxicology systems be tested against these structure.
The role of dicarbonyl compounds in non-enzymatic crosslinking: a structure-activity study.
Meade SJ, Miller AG, Gerrard JA. Department of Plant and Microbial Sciences, University of Canterbury, Private Bag 4800, Christchurch, New Zealand.
The Maillard reaction is a complex network of reactions that has been shown to result in the non-enzymatic crosslinking of proteins. Recent attention has focussed on the role of alpha-dicarbonyl compounds as important in vivo contributors to protein crosslinking but, despite extensive research, the molecular mechanisms of the crosslinking reaction remain open to conjecture. In particular, no relationship between the structure of the carbonyl-containing compounds and their activity as crosslinking agents has been established. In an effort to elucidate a structure-reactivity relationship, a wide range of dicarbonyl compounds, including linear, cyclic, di-aldehyde and di-ketone compounds, were reacted with the model protein ribonuclease A and their crosslinking activity assessed. Methylglyoxal and glutaraldehyde were found to be the most efficient crosslinkers, whilst closely related molecules effected crosslinking at a much lower rate. Cyclopentan-1,2-dione was also shown to be a reactive crosslinking agent. The efficiency of methylglyoxal and glutaraldehyde at crosslinking is thought to be related to their ability to form stable heterocyclic compounds that are the basis of protein crosslinks. The reasons for the striking reactivity of these two compounds, compared to closely related structures is explained by subtle balances between competing pathways in a complex reaction network.
>>>>>>>>>>>>>>>>>>>>>>>>>>>>
BrooklynDodger(s) comments: Most toxicology textbooks and writings about risk assessment mention "structure activity relationships" as a method of hazard identification. There is some funding for computational toxicology. The Dodger(s) think(s) this is wasted space and money in occupational, environmental (including food) toxicology. It reflects the pharmacology roots of many toxicologists; pharmacologists who use this for suggesting "me too" drugs. Some of the key agents identified in recent years demonstrate the failure of this approach to spur research before the fact. Maybe the best known is n-hexane, methyl-n-butylketone (2-hexanone), 2,5-hexadione sequence causing peripheral neuropathy. The Dodger(s) haven't seen a convincing explanation of why n-heptane is not known to cause the peripheral neuropathy demonstrated in the laboratory after people got sick. Butadiene, chloroprene and isoprene (1,3 dienes) are carcinogenic by inhalation, especially butadiene with great potency.
Which brings us to popcorn lung. When diacetyl (2,3-butadiONE) was first proposed as a cause of popcorn lung, the Dodger(s) were skeptical. To a toxicologist, it didn't look like much, it was GRAS, and it was even in beer. So the issue is whether the toxicity of diacetyl could be anticipated from structure activity. The alpha, beta dione structure could suggest some kind of electrocyclic reaction, but it turns out that a much simpler effect was known, the Maillard Reaction, well known in the food chemistry circles. The Dodger(s) didn't find any special reference to diacetyl in the publication abstracted above.
The Dodger(s) would propose that chemicals containing the 1,3-diene or the 2,4-dione moiety be considered toxic until proven innocent. And that future computational toxicology systems be tested against these structure.
Saturday, January 10, 2009
A No Effect Level for Particulate Air Pollution Exposure Well Below Established Air Quality Standards
Inhalation Toxicology, Volume 21, Issue 1 January 2009 , pages 38 - 47
Effects of Ambient Air Particulate Exposure on Blood-Gas Barrier Permeability and Lung Function
Authors: Elvira Vaclavik Bruner a; Jann Mortensen b; Peter Mller a; Alfred Bernard c; Peter Vinzents a; Peter Whlin d; Marianne Glasius d; Steffen Loft a
Affiliations:
a Institute of Public Health, Department of Environmental Health, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
b Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Faculty of Health Sciences, University hospital of Copenhagen, Copenhagen, Denmark
c School of Public Health. Faculty of Medicine, Catholic University of Louvain, Louvain, Belgium
d Department of Atmospheric Environment, National Environmental Research Institute, Roskilde, Denmark
Abstract
Particulate air pollution is associated with increased risk of pulmonary diseases and detrimental outcomes related to the cardiovascular system, including altered vessel functions. This study's objective was too evaluate the effects of ambient particle exposure on the blood-gas permeability, lung function and Clara cell 16 (CC16) protein release in healthy young subjects. Twenty-nine nonsmokers participated in a randomized, two-factor crossover study with or without biking exercise for 180 min and with 24-h exposure to particle-rich (6169-15,362 particles/cm3; 7.0-11.6 μg/m3 PM2.5; 7.5-15.8 μg/m3 PM10-2.5) or filtered (91-542 particles/cm3) air collected above a busy street. The clearance rate of aerosolized 99mTc-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) was measured as an index for the alveolar epithelial membrane integrity and permeability of the lung blood-gas barrier after rush-hour exposure. Lung function was assessed using body plethysmography, flow-volume curves, and measurements of the diffusion capacity of carbon monoxide. CC16 was measured in plasma and urine as another marker of alveolar integrity. Particulate matter exposure had no significant effect on the epithelial membrane integrity using the methods available in this study. Exercise increased the clearance rate of 99mTc-DTPA indicated by a 6.8% (95% CI: 0.4-12.8%) shorter half-life and this was more pronounced in men than women. Neither particulate matter exposure nor exercise had an effect on the concentration of CC16 in plasma and urine or on the static and dynamic volumes or ventilation distribution of the lungs. The study thus demonstrates increased permeability of the alveolar blood-gas barrier following moderate exercise, whereas exposure to ambient levels of urban air particles has no detectable effects on the alveolar blood-gas barrier or lung function.
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BrooklynDodger(s) comment: What do the Dodger(s) intend by posting a null study? Sometimes a No Observed Adverse Effect Level is useful in risk assessment. The Dodger(s) remind(s) the reader that a robust NOAEL below a LOAEL corresponds to a 10% attack rate. Null studies are attached to an exposure level and regimen.
Clara cells are all the rage these days. The Clara cell resident in the lung has phagocytic, secretory and P450 type activity. The Dodger(s) think of Clara cells as being like Kuppfer cells in the liver - a population not thought of 30 years ago which is now likely involved in chemical injury. Differences in Clara cell activity figure in the Houdini Risk Assessment of solvent vapors which are consistently carcinogenic in the mouse lung but not the rat.
The NOAEL for increased release of clara cell secretory in healthy, non smoking human volunteers is an exposure for 24 hours to ambient type particulate less than 12 ug/m^3 for PM2.5 and maybe 27 ug/m^3 for PM10. The current EPA NAAQS for 24-hour exposures are 35 ug/m^3 and 150 ug/m^3. This appears to have been some pretty clean days in Copenhagen. The Dodger(s) couldn't get the full text because full text Inhalation Toxicology is hard to find. So the Dodger(s) don't know the effect level for increased release of this protein, if it is known.
Effects of Ambient Air Particulate Exposure on Blood-Gas Barrier Permeability and Lung Function
Authors: Elvira Vaclavik Bruner a; Jann Mortensen b; Peter Mller a; Alfred Bernard c; Peter Vinzents a; Peter Whlin d; Marianne Glasius d; Steffen Loft a
Affiliations:
a Institute of Public Health, Department of Environmental Health, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
b Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, Faculty of Health Sciences, University hospital of Copenhagen, Copenhagen, Denmark
c School of Public Health. Faculty of Medicine, Catholic University of Louvain, Louvain, Belgium
d Department of Atmospheric Environment, National Environmental Research Institute, Roskilde, Denmark
Abstract
Particulate air pollution is associated with increased risk of pulmonary diseases and detrimental outcomes related to the cardiovascular system, including altered vessel functions. This study's objective was too evaluate the effects of ambient particle exposure on the blood-gas permeability, lung function and Clara cell 16 (CC16) protein release in healthy young subjects. Twenty-nine nonsmokers participated in a randomized, two-factor crossover study with or without biking exercise for 180 min and with 24-h exposure to particle-rich (6169-15,362 particles/cm3; 7.0-11.6 μg/m3 PM2.5; 7.5-15.8 μg/m3 PM10-2.5) or filtered (91-542 particles/cm3) air collected above a busy street. The clearance rate of aerosolized 99mTc-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) was measured as an index for the alveolar epithelial membrane integrity and permeability of the lung blood-gas barrier after rush-hour exposure. Lung function was assessed using body plethysmography, flow-volume curves, and measurements of the diffusion capacity of carbon monoxide. CC16 was measured in plasma and urine as another marker of alveolar integrity. Particulate matter exposure had no significant effect on the epithelial membrane integrity using the methods available in this study. Exercise increased the clearance rate of 99mTc-DTPA indicated by a 6.8% (95% CI: 0.4-12.8%) shorter half-life and this was more pronounced in men than women. Neither particulate matter exposure nor exercise had an effect on the concentration of CC16 in plasma and urine or on the static and dynamic volumes or ventilation distribution of the lungs. The study thus demonstrates increased permeability of the alveolar blood-gas barrier following moderate exercise, whereas exposure to ambient levels of urban air particles has no detectable effects on the alveolar blood-gas barrier or lung function.
>>>>>>>>>>>>>>
BrooklynDodger(s) comment: What do the Dodger(s) intend by posting a null study? Sometimes a No Observed Adverse Effect Level is useful in risk assessment. The Dodger(s) remind(s) the reader that a robust NOAEL below a LOAEL corresponds to a 10% attack rate. Null studies are attached to an exposure level and regimen.
Clara cells are all the rage these days. The Clara cell resident in the lung has phagocytic, secretory and P450 type activity. The Dodger(s) think of Clara cells as being like Kuppfer cells in the liver - a population not thought of 30 years ago which is now likely involved in chemical injury. Differences in Clara cell activity figure in the Houdini Risk Assessment of solvent vapors which are consistently carcinogenic in the mouse lung but not the rat.
The NOAEL for increased release of clara cell secretory in healthy, non smoking human volunteers is an exposure for 24 hours to ambient type particulate less than 12 ug/m^3 for PM2.5 and maybe 27 ug/m^3 for PM10. The current EPA NAAQS for 24-hour exposures are 35 ug/m^3 and 150 ug/m^3. This appears to have been some pretty clean days in Copenhagen. The Dodger(s) couldn't get the full text because full text Inhalation Toxicology is hard to find. So the Dodger(s) don't know the effect level for increased release of this protein, if it is known.
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